Dental, Particularly Remineralizing Composition, Effective for Pain Sensitive Teeth, and Dental Particles, Particularly for Said Composition

ABSTRACT

The invention relates to a dental, particularly a remineralizing composition, effective for pain sensitive teeth, such as toothpaste, tooth powder, mouth wash, chewing gum, dental formulations or the like, comprising spherical dental particles having a particle size between 0.1 and 2 μm made of silica gel in an one-part combination, comprising at least one combination agent selected from at least a phosphate, a oxide, a further oxygen-containing compound, a hydroxide, hydrogen carbonate or carbonate of the metals of groups II and III of the periodic system, as well as zinc or tin, wherein the dental particles are present in an amount such that the SiO 2  amount resulting from the silica gel is less than 1 wt. %.

The invention relates to dental, notably remineralising and desensitising composition as toothpaste, tooth powder, mouthwash, chewing gum, therapeutic varnishes etc. Furthermore, the invention relates to dental particles, notably for the said compositions.

The surfaces of teeth are in a constant balance between the loss and gain of minerals. This process is partially kept in balance by the chemical composition of saliva and the extra-cellular fluid. Disruption of the tooth surface integrity can occur by acidic food and beverages, bacterial challenge and erosion by exaggerated tooth brushing or grinding of the teeth.

These processes are accompanied by a demineralisation of the exposed tooth surfaces leading to clinical conditions such as dentine hypersensitivity and caries.

Enamel mainly consists of inorganic mineral substance (95% by weight=86% by volume). It does not consist of pure hydroxy apatite but of mixed apatite and defect apatite. In mixed apatite calcium can be replaced by magnesium, strontium and other divalent cations. PO₄ ³⁻ can be replaced by HPO4²⁻, H2PO4⁻, CO3²⁻ or HCO3⁻. In defect apatite the location of calcium in the lattice remains empty.

In saliva, minerals like calcium and phosphates are dissolved. When pH drops in plaque and saliva the dissolved phosphate ions are protonated and thus removed from the equilibrium. In order to re-establish the equilibrium apatite crystals have to be dissolved from the enamel. Thus a demineralisation of the enamel (initial lesion) takes place. With raising pH the reverse reaction occurs. Due to the over-saturation of the saliva with apatite remineralisation takes place.

In an initial lesion immediately above the sound enamel a translucent zone exists. It contains about 1% of pores. Sound enamel only contains about 0.1% of pores. These pores or micro-channels have a diameter of 0.5 to 1.5 μm and a depth of 100 μm, which eventually allow bacterial invasion.

When challenged by demineralisation and bacteria caries can result in enamel and dentine. Dentine hypersensitivity is a clinical condition defined by an exaggerated response of the pulpal nerve to stimuli like cold, sweet, etc. The basis of this condition is exposed dentine due to erosion of the enamel/cementum, due to gingival recession and/or periodontal surgery.

The mineral proportion of dentin represents only 70% by weight or 45% by volume. Dissolution of the dentin starts already at a higher pH than the dissolution of enamel and it is much more porous. Therefore caries spreads more rapidly upon reaching the dentin than in enamel. The body reacts with the formation of sclerosing dentin as an attempt to build a barrier between caries and pulp. Minerals are deposited in the tubules inhibiting the diffusion of acids, toxins and proteolytic enzymes as well as bacteria.

Many attempts have been made to treat dentine hypersensitivity. According to the prior art, one approach is to reduce the excitability of the pulp by changes of the chemical environment of the nerve. Therefore agents are used which make the tooth less sensitive. According to the prior art several nerve desensitising agents are known. For this purpose predominantly potassium nitrate is used which is deployed in commercial toothpastes for the desensitisation of teeth (U.S. Pat. Nos. 3,863,006, 4,009,327 and 4,751,072). In these patents mainly formulations resp. compositions containing potassium salts including potassium bicarbonate and potassium chloride are described.

An additional attempt according to the prior art has been made to control dentine hypersensitivity by using agents obtunding the tubules partially or completely. These agents are described as tubule blocking agents. In U.S. Pat. No. 4,990,327 a desensitisation of teeth with strontium and fluoride ions has been disclosed. Furthermore, U.S. Pat. No. 3,888,976 discloses the treatment of sensitive teeth by using zinc and strontium ions. U.S. Pat. No. 5,211,937 reports the use of charged polystyrene beads as chemically inert agent blocking mechanically the surface of tubules, U.S. Pat. Nos. 4,634,589 and 4,710,372 deal with the use of clays like laponite or hectorite to obtund the tubules. U.S. Pat. No. 5,270,031 discloses the use of polyacrylic acids with a typical molecular weight of approximately 450.000 to 4.000.000 used as tubule blocking agents. Furthermore, U.S. Pat. No. 4,362,713 discloses the use of water-soluble or water-swelling poly-electrolytes and their salts as tubule blocking agents.

Further, in the prior art, the use of substrates as spherical micro-particles is known, on which active therapeutic substances are adsorbed by chemical, electrostatic or ionic bonding, to accelerate the wound healing rate or bone regeneration. As a result active chemical compounds can be released in a controlled way. These so-called micro-spheres can be hollow or massive; the chemical substance can be adsorbed on the surface or encapsulated within the sphere.

From U.S. Pat. No. 5,037,639 the use of amorphous, thus non-spherical calcium compounds is known which are applied to the dentinal structure of the teeth supposedly leading to apatite formation in situ. This apatite formation supposedly leads to a remineralisation of the teeth and a reduction of hypersensitivity.

DE 695 24 747 T2 contains an extensive review of the prior art regarding the reduction of hypersensitivity with sub-micron particles and discloses the use of cationic charged colloidal particles in an aqueous environment. It is suggested for example to use commercially available non-spherical silica with an average particle size of 20 nm with a coating of aluminium oxide of a particle size of 2 nm. This product consists of an aqueous, colloidal dispersion of the aluminium sub-micron particles. For dental compositions the compound should be used on average in amounts of 0.1% to 10% by weight.

The thesis of Gerd Fischer titled: Development, characterisation and application of novel hybrid materials presented to the Faculty of Chemistry and Pharmaceutics of the Eberhard-Karls University of Tuebingen, 2004, describes the controlled synthesis of mono-disperse spherical silica particles with a diameter between 0.2 and 1.8 μm according to the Sol-Gel-Process and their combination with other materials. Among others the coating and the co-condensation with hydroxyapatite resulting in mono-disperse particles with diameters of 1.5 and 3.5 μm is disclosed. Within the combination silica was used to generate shape and size whereas hydroxyapatite was used to introduce similarity to the dental material intending the restoration of enamel loss through the effect of the hydroxyapatite.

In EP 0 216 278 B1 the production of non-porous, mono-disperse spherical silica particles of the Sol-Gel Process, notably with a particle size of 0.05-10 μm is disclosed.

DE 103 30 204 A1 discloses a sol-gel-process for the preparation of non-porous, spherical, mono-disperse silica particles notably with a particle size between 0.2 and 1.2 μm carrying molecules immobilised by so-called spacers at their surface.

Furthermore WO 02/30380 A1 discloses the desensitisation of teeth among others by inducing a regeneration of bone materials to obtund the dentin tubules. Among others the use of hydroxyapatite, fluoroapatite, chloroapatite, tricalcium phosphate and other substrates based on calcium phosphate is disclosed. These substances can be attached to a silica substrate with a particle size of the substrate<10 microns. The porous or non-porous particles carrying the desensitising agents are present in concentrations between 1% and 70% by weight in dental resp. desensitising compositions like toothpaste, mouthwash, tooth powder, varnishes, chewing gum etc. The compositions may additionally contain typical ingredients like abrasives or additional desensitising or otherwise effective ingredients.

Disadvantageous for all these agents for the desensitisation of teeth according to prior art is that they only temporarily alleviate the symptoms without leading to a lasting obturation of open tubules by incorporation and remineralisation i.e. crystal growth since they are surface acting only. Only a lasting occlusion of the tubules can prevent the occurrence of hypersensitive teeth.

These surface acting substances according to the prior art are not able to achieve this. These substances penetrate the tubules only insufficiently or not at all and cannot influence i.e. inhibit the nervous transmission. Because of the chemical structure of these substances they cannot or only insufficiently be incorporated into the existing tooth structure to generate a sufficient remineralisation of the teeth and an obturation of the tubules.

This not only applies for dentin but also for enamel. The prior art discloses a number of patents claiming remineralisation of enamel lesions and prevention of caries. U.S. Pat. No. 3,175,951 discloses for instance the use of fluorides to fight cavities.

In vitro and in vivo it could be shown that initial lesions can be at least partly remineralised and where applicable even completely restored. Fluoride can influence the misbalanced interaction between de- and remineralisation in favour of the remineralisation. Via diffusion channels fluoride penetrates into the enamel. By that fluoride is bound to the enamel forming fluoroapatite and fluoridated hydroxyapatite. In the outer layer of the enamel less than 10% of the hydroxyl groups are replaced by fluoride, in a depth of 50 μm only 1%. While in saliva hydroxyapatite is demineralised already at a pH of 5.5, this happens with fluoroapatite not until 4.6. For the reverse reaction i.e. remineralisation it means that in the presence of sufficient fluoride remineralisation can occur already at a pH of 4.6 whilst without fluoride this occurs not until a pH 5.5.

Another method to promote remineralisation is the use of soluble calcium salts. U.S. Pat. No. 4,080,440 discloses the use of soluble calcium salts with soluble fluorides for the remineralisation of enamel. U.S. Pat. No. 4,048,300 discloses the use of calcium phosphates like fluoroapatite, fluorohydroxyapatite and hydroxyapatite as well as monofluorophosphate, carbonate and di-valent cations like zinc.

U.S. Pat. Nos. 6,733,818 and 6,846,500 combine amorphous calcium phosphate with casein-phosphopeptide and bicarbonate as chewing gums or confectionary. U.S. Pat. Nos. 5,858,333 and 5,603,922 disclose the use of products in dual chamber tubes one chamber containing soluble calcium salts and the other phosphates and fluoride mixing upon simultaneous squeezing from the tube and leading to remineralisation in situ. U.S. Pat. Nos. 5,534,244, 5,437,857 and 5,460,803 disclose the use of amorphous strontium and calcium phosphates with or without fluoride for remineralisation of enamel. U.S. Pat. No. 6,521,215 discloses advantageous compositions and methods for bleaching and remineralisation of teeth, against hypersensitive teeth and for the treatment of caries with a soluble calcium phosphate consisting of one or more compounds of the group monocalcium phosphate, tricalcium phosphate and tetracalcium phosphate. U.S. Pat. No. 4,923,683 discloses the use of micro-encapsulated hydroxyapatite and/or fluoride.

Purpose of the invention is to provide dental compositions and particles which on the one hand can penetrate the tooth surface sufficiently to efficiently contribute to the remineralisation of the tooth structure of enamel and dentin and/or on the other hand facilitate an obstruction of transport of matter and transmission of signals within the tubules and a subsequent desensitisation of the teeth by remineralisation and crystal growth within pores of the enamel as well as in dentin tubules and by blocking the tubules. On the one hand through this remineralisation of dentine hypersensitivity will be reduced and on the other hand the original tooth structure will be maintained and/or restored after a cariogenic challenge. Through remineralisation of enamel through the precipitation of the said dental particles on the surface and in the pores (microchannels) of the enamel the original tooth structure will be maintained and/or restored after a cariogenic challenge. This also prevents other dental disorders which are based on defects of the mineral structure like erosions for example and others.

This problem is solved by the characteristics of the claims 1 and 14. Advantageous detailed characteristics of the invention are listed in the sub-claims.

Accordingly, the invention provides a dental composition containing notably non-porous, spherical particles, notably mono-disperse, prepared by a combination in the form of a coating or co-condensation or mixture with a combination agent selected from at least one water insoluble phosphate of the metals of the II. and III. group of the periodic system as well as zinc and tin or with at least one water insoluble oxygen containing compound, a hydroxide, a hydrogen carbonate or a carbonate of the same groups, spherical, preferably non-porous silica particles notably of defined uniform particle size and notably therapeutically active dental particles of a particle size between 0.1 and 2 μm, and notably between 0.5 and 1.5 μm and in fact only with a SiO₂ amount—resulting from silica—below 1% by weight, notably from 0.1 to 0.9% by weight and most notably between 0.3 and 0.7% by weight. Water insoluble for the present invention means no absolute insolubility in water but only a slight solubility where under physiological conditions small amounts of ions can be released and delivered for the above described processes of remineralisation

For the coating and the co-condensation the preparation of the said dental particles is known. The third preparation method for the combination consists of a mixing of the particles to form granules where preferably mono-disperse particles of silica are combined with mono-disperse particles of the phosphates for example of the same size or a water insoluble oxygen containing compound, a hydroxide, a hydrogen carbonate or a carbonate mixed for example in a granule-mixer. Particle sizes between 0.05 and 1.2 μm and notably between 0.1 to 1.0 μm are mixed and granulated to dental particles of the said size.

Preferably, at least one apatite, notably from the metals calcium, magnesium and strontium notably the hydroxyapatite is combined with the silica particles to form the dental particles. Furthermore the following phosphates like fluoroapatite, chloroapatite tricalcium phosphate and other compounds based on calcium phosphate like monocalcium phosphate, tricalcium phosphate and tetracalcium phosphate are suitable. Further suitable combinations result from the said oxygen containing compounds like MgO, SrO, Ba0, Al₂O₃, ZnO, SnO, SnO2 but also borates, aluminates etc. as well as hydroxides, hydrogen carbonates and carbonates of these metals

The dental particles notably the hydroxyapatites, phosphates, oxygen containing compounds, hydroxides, hydrogen carbonates and carbonates containing dental particles are contained in the finished dental composition in amounts of 0.1 to 10%, notably from 1 to 5%. The dental particles contain the SiO₂ proportions of the silica particles in amounts of 10 to 90%, notably from 30 to 70%.

Missing proportions to add up to 100% in the dental particles consist of the other above-mentioned desensitising agents like hydroxyapatite, strontium hydroxyapatite, magnesium hydroxyapatite or the other phosphates, the oxygen containing compounds, hydroxides, hydrogen carbonates and carbonates of the metals of the II. and III. group of the periodic system as well as zinc and tin.

Notably particles are prepared with a bulk density between 1.0 and 4.0 notably between 1.5 and 3 g/cm³. Bulk density is determined according to DIN 53 912.

It has been shown that the said dental compositions result in a regular adhesion or incorporation of the spherical dental particles onto or into the tooth surface, into the tooth structure or into the dentin tubules through an interaction between the silica with the combination material which cannot be achieved through the separate use of the phosphate or silica particles or in combination with other substrates. The regular adhesion or incorporation of the spherical particles as shown in FIGS. 1 and 2, occurs obviously through the interaction with the surface charge of the tooth which is characterised by Van-der-Waals forces, ionic bonding and by the interaction with the surface charge of the tubules and the interaction with the extra-cellular dentinal fluid as well as with a combination of all three effects. In each case a surprisingly strong immobilisation resp. adhesion of the dental particles is a condition for the effect upon the damaged tooth structure.

FIG. 1 shows a fracture of a dentin disc as well as dental particles according to the invention adhered and incorporated as well as tubules 5.

FIG. 2 shows a vertical view upon the surface of a dentin disc with patent tubules 5.

The uniqueness of the charge of the said spherical particles is caused by the geometry of the spheres producing a piezoelectric effect and by the ionic compounds combined with the SiO₂ particles making up for the composition of the spheres.

Surprisingly, low concentrations of the silica i.e., less than 1% in the finished product optimizes the electrostatic interaction with the respective tooth surfaces. This is attributed to the geometry of the spherical particles producing an electrostatic effect whereby a higher concentration or proportion of silica diminishes the electrostatic interaction of the spheres with the tooth surfaces.

In addition to the electrostatic interaction the cations present in the spherical particles serve as a reservoir or crystallisation nidus for the formation of cation dependent forms of hydroxyapatite. This cation dependency is seen with calcium being deposited preferably on the tooth surface whereas other cations such as Sr, Mg, being preferably deposited within the dentinal tubule.

The spherical particles are retained at the respective tooth surfaces by their inherent charges as described above. These spherical particles also fill voids in the enamel/dentine surface. Furthermore a physical migration of the said spherical particles into the enamel pores and the dentinal tubules occurs. The spherical particles with their unique geometry and electrical charge characteristic adhere to and are retained within the enamel pores and dentinal tubule. By being retained in the dentinal tubules the spherical particles interact with the dentinal fluid by adsorbing it to their surface thereby inhibiting or reducing the dentinal fluid turnover rate. By reducing dentinal fluid flow due to changes on the surface from external sources the odontoblastic cell body and its processes do not undergo a perturbation and subsequently do not trigger the nerve action potential.

The selection of the spherical dental particles guarantees the densest packing to occlude the enamel pores and dentinal tubules based on the spherical shape notably when using spherical dental particles of different diameters according to the invention as well as the above mentioned favourable distribution of the electrical surface charge of the dental particles which notably guarantees the immobilisation.

According to the invention, dental particles of different diameters are combined for the dental compositions. Also according to the invention dental particles which contain different combination agents in a dental composition can be used. Also in this case dental particles of different diameters can be used.

The particles are unique regarding density and geometry providing penetration into pores and tubules and also a certain retention time for the particle to act as a nidus for efficacy desensitising teeth as well as remineralising the tooth surface area to maintain surface integrity.

The different diameter and density of the spherical diameters are in line with different pore sizes of the dentine/enamel surface depending on the depth of penetration of the noxa, age of the individual and location of the tooth.

This invention differs from the prior art by the fact that the geometry of the particles as spherical particles as well as the range of the particle sizes can be optimised that the different sizes of the pores and tubules within the tooth surface can be taken into account. The said particles can penetrate the tooth surface, thus achieving a retention time sufficient for the process of remineralisation and for achieving therapeutic efficacy. 

1. Dental, notably remineralising and desensitising composition like toothpaste, tooth powder, mouthwash, chewing gum, professional formulations etc. featuring a) spherical non porous dental particles b) from silica with c) particle sizes between 0.1 and 2 μm d) in combination with e) at least one water insoluble combination agent f) releasing under physiological conditions small amounts of ions for a remineralisation of the dental material g) chosen from at least one phosphate, one oxide one other oxygen containing compound one hydroxide one hydrogen carbonate or carbonate of the metals of the II. and III. group of the periodic system as well as zinc and tin h) where the dental particles are contained in an amount that the amount of SiO₂ from the silica is below 1% by weight. i) dental particles contained in an amount of 0.1 to 10% by weight and j) dental particles containing SiO₂ from silica in amounts of 10 to 90% where missing percentages to 100% stem from combination agents.
 2. Composition of claim 1 characterised by the amount of SiO₂ being between 0.1 and 0.9% notably between 0.3 and 0.7%
 3. Composition of claim 1 or 2 characterised by the particle size of the dental particles being between 0.5 and 1.5 μm.
 4. Composition of one or more of the claims 1 to 3 characterised by the combination of the dental particles obtained by coating, co-condensation or mixing and granulation of silica with at least one combination agent notably a phosphate, an oxide or another oxygen containing anion, a hydroxide, a hydrogen carbonate or a carbonate.
 5. Composition of one or more of the claims 1 to 4 characterised by the spherical dental particles being nearly non-porous.
 6. Composition of one or more of the claims 1 to 5 characterised by the particles being mono-disperse
 7. Composition of one or more of the claims 4 to 6 characterised by the particle size of the silica particles within the coated or mixed dental particles being between 0.05 and 1,5 μm notably between 0.1 and 1.0 μm.
 8. Composition of one or more of the claims 4 to 7 characterised by the silica and phosphate or oxide or hydroxide or carbonate particles being of the same or of different sizes within in the mixed and granulated particles.
 9. Composition of one or more of the claims 4 to 8 characterised by the silica particles being in a mono-disperse form or a mixture of different sizes.
 10. Composition of one or more of the claims 1 to 9 characterised by the phosphate being at least one apatite notably of the metals Ca, Mg, Sr, Ba, Al, B, Zn and Sn and notably being a hydroxyapatite.
 11. Composition of one or more of the claims 1 to 10 characterised by the dental particles being contained in the dental composition in amounts of 1 to 5% by weight.
 12. Composition of one or more of the claims 1 to 11 characterised by the amount of silica in the dental particles being between 30 and 70% by weight.
 13. Composition of one or more of the claims 1 to 12 characterised by the bulk density of the dental particles being between 1.0 and 4.0 g/cm³ notably between 1.5 and 3.0 g/cm³.
 14. Spherical dental particles notably for dental compositions of one or more of the claims 1 to 13 characterised by silica in combination with at least one combination agent selected from at least one phosphate, oxide, another oxygen containing compound, a hydroxide, a hydrogen carbonate or a carbonate of the metals of the II. and III. group of the periodic system as well as zinc and tin—except dental particles coated with hydroxyapatite or prepared through co-condensation with hydroxyapatite.
 15. Particles of claim 14 characterised by the particles sizes being between 0.1 and 2.0 μm notably between 0.5 and 1.5 μm.
 16. Particles of claim 14 and/or 15 characterised by a combination of the dental particles prepared by coating or co-condensation or mixing and granulation of silica with at least one combination agent notably a phosphate, an oxide, another oxygen containing anion, a hydroxide, a hydrogen carbonate or a carbonate.
 17. Particles of one or more of the claims 14 to 16 characterised by the spherical dental particles being nearly non-porous.
 18. Particles of one or more of the claims 14 to 17 characterised by the spherical particles being mono-disperse.
 19. Particles of one or more of the claims 14 to 18 characterised by the particle size of the silica particles within the coated or mixed dental particles being between 0.05 and 1.5 μm and notably between 0.1 and 1.0 μm.
 20. Particles of one or more of the claims 14 to 19 characterised by the silica and phosphate particles within the mixed and granulated particles are of the same or of different sizes.
 21. Particles of claim 19 and/or 20 characterised by the silica particles being mono-disperse.
 22. Particles of one or more of the claims 19 to 21 characterised by the combination agent in the granulated combination being at least an apatite, notably a hydroxyapatite, an oxygen containing compound, a hydroxide, a hydrogen carbonate or a carbonate.
 23. Particles of one or more of the claims 14 to 22 characterised by the amount of silica in the dental particles being between 10 and 90% notably between 30 and 70% by weight.
 24. Particles of one or more of the claims 14 to 23 characterised by the bulk density being between 1.0 and 4.0 g/cm³ notably between 1.5 and 3.0 g/cm³.
 25. Use of dental particles of one or more of the claims 14 to 24 in a dental composition of one or more of the claims 1 to 13 with different diameters and different combination agents. 